Recent work in this laboratory on the oxidation and reduction of vertebrate cytochrome c by inorganic oxidants and reductants strongly suggests the electron transfer takes place at the exposed heme edge. It has been found that reduction is preceeded by displacement of a bound anion apparently near the site of electron transfer. In addition, we have found the ATP binds strongly at or near the anion binding site competitively inhibiting the reduction by ferrocyanide. This result suggests the possibility of control of the rate of electron transport by a product of the process. The work proposed here covers two general areas: 1) It is proposed to extend the anion binding work in an effort to determine the specific amino acid side chain involved in anion binding. 2) We are investigating the transient kinetics of the interaction of vertebrate cytochrome c with beef heart cytochrome oxidase and microsomal cytochrome b5. These latter studies are designed to test our model for the reaction of inorganic oxidants and reductants on a more physiological system and to obtain information fundamental to the understanding in molecular terms of the factors mediating protein- protein interactions.